To evaluate the reproducibility of plaque quantification from serial cardiac computed tomography (CCTA) scans by a systematic side-by-side approach using validated AI-enabled software with both scan-specific and fixed attenuation thresholds. Thirty participants from two centers underwent serial CCTA within a short timeframe (median 6 days [IQR 0–30]). Volumes and burden (defined as plaque volume indexed by vessel volume) of total plaque (TP), calcified plaque (CP), non-calcified plaque (NCP), and low-density NCP (LD-NCP) were quantified per-patient while comparing the serial scans side-by-side. Analyses were done by two assessors using consensus readings to reduce individual bias, and inter-scan differences were compared using mean differences and the repeatability coefficient (RC, defined as 1.96 × standard deviation). Mean age was 59 years (70

Importance The extent and severity of coronary artery disease (CAD) on coronary CT angiography (CCTA) is predictive of mortality, cardiovascular death, and non-fatal myocardial infarction in both men and women; however, associations of various measures of coronary plaque burden with prognosis in younger women and men has had little study. Objective To compare prognostic significance of CAD plaque burden and distribution on CCTA in women and men <60. Design 3813 consecutive patients (age: 49.4±8.1 years, 36% women) without CAD history who underwent CCTA (2007-2019) with clinical follow-up. Setting Single academic medical center Interventions None Main Outcomes CCTA plaque burden was assessed by stenosis severity, segment involvement score (SIS), segment stenosis score (SSS), and coronary artery calcium (CAC) scores. Primary endpoint: all-cause mortality (ACM); secondary outcome: ACM or non-fatal MI (NFMI). Results 180 (4.7%) ACM occurred over a median of 7.4 years, Severity of stenosis, SIS, SSS and extent of CAC were higher in men compared to women (all p<0.001). In multivariable Cox models, there were significant interactions between sex and all CCTA measures, with women having higher risk than men of ACM with increase of each plaque burden measure compared to men: coronary stenosis (CAD≥50% HR 6.52 vs 1.86, interaction p=0.021), SIS (SIS>4 HR 6.94 vs 1.68, interaction p=0.006), SSS (SSS>6 HR 7.91 vs 1.79, interaction p=0.006) and CAC (CAC>300 HR 9.62 vs 1.82, interaction p=0.004). All plaque burden measures discriminated events in women better than men, with C-statistics for multivariable models ranging from 0.729-0.760 in women, compared to 0.674-0.690 in men. Findings were similar for ACM/NFMI. Conclusions Prognostic significance of multiple measures of plaque burden identified by CCTA had greater prognostic impact in younger women, compared with younger men. Trial Registration NA

OBJECTIVE:To explore differences in prevalence and prognosis associated with reduced myocardial flow reserve (MFR) in patients without known coronary artery disease (CAD) based on diabetes status. METHODS:Of 2639 patients without known CAD who underwent rubidium positron emission tomography myocardial perfusion imaging (MPI), 818 patients (31%) had diabetes. Reduced MFR was defined as MFR <2.0. Coronary artery calcium (CAC) score was categorized as 0, 1-99, 100-399, and ≥400. Ischemic total perfusion deficit (TPD) was categorized as <1%, 1-<5%, and ≥5%. Outcome variables were all-cause death (ACD) and non-fatal myocardial infarction (MI). RESULTS:During the median follow-up of 4.1 years, 574 (21.8%) ACD/MI occurred (204 [25.1%] diabetic patients, 370 [20.3%] nondiabetic patients). In multivariable Cox analysis, reduced MFR was associated with increased ACD/MI in patients with diabetes (per .1 decrease: HR: 1.04, 95% CI: 1.02-1.06, P < .001) and patients without diabetes (per .1 decrease: HR: 1.03, 95% CI: 1.02-1.04, P < .001). No interaction existed between diabetes and MFR for ACD/MI risk regardless of CAC or ischemic burden (all P > .05). Adding MFR to the risk prediction model of clinical, conventional MPI findings, and CAC improved the discrimination for clinical outcomes in both groups (DM: .003, non-DM: <.001, respectively). CONCLUSION:Reduced MFR was more common in patients with diabetes and an important independent prognostic marker over CAC and clinical variables. The association between MFR and ACD/MI risk did not differ between patients with and without diabetes who had no prior CAD, regardless of CAC and ischemic burden.

BACKGROUND:The new artificial intelligence-based software, Roadmap (HeartFlow), may assist in evaluating coronary artery stenosis during cardiac computed tomography (CT) for transcatheter aortic valve replacement (TAVR). METHODS:Consecutive TAVR candidates who underwent both cardiac CT angiography (CTA) and invasive coronary angiography were enrolled. We evaluated the ability of three methods to predict obstructive coronary artery disease (CAD), defined as ≥50 ​% stenosis on quantitative coronary angiography (QCA), and the need for percutaneous coronary intervention (PCI) within one year: Roadmap, clinician CT specialists with Roadmap, and CT specialists alone. RESULTS:The area under the curve (AUC) for predicting QCA ≥50 ​% stenosis was similar for CT specialists with or without Roadmap (0.93 [0.85-0.97] vs. 0.94 [0.88-0.98], p ​= ​0.82), both significantly higher than Roadmap alone (all p ​< ​0.05). For PCI prediction, no significant differences were found between QCA and CT specialists, with or without Roadmap, while Roadmap's AUC was lower (all p ​< ​0.05). The negative predictive value (NPV) of CT specialists with Roadmap for ≥50 ​% stenosis was 97 ​%, and for PCI prediction, the NPV was comparable to QCA (p ​= ​1.00). In contrast, the positive predictive value (PPV) of Roadmap alone for ≥50 ​% stenosis was 49 ​%, the lowest among all approaches, with a similar trend observed for PCI prediction. CONCLUSIONS:While Roadmap alone is insufficient for clinical decision-making due to low PPV, Roadmap may serve as a "second observer", providing a supportive tool for CT specialists by flagging lesions for careful review, thereby enhancing workflow efficiency and maintaining high diagnostic accuracy with excellent NPV.

BACKGROUND:We investigated whether the shape of arterial blood input curves affects the diagnostic performance of myocardial blood flow (MBF) on rubidium-82 (82Rb) positron emission tomography (PET) myocardial perfusion imaging (MPI) for obstructive coronary artery disease (CAD). METHODS AND RESULTS:We retrospectively enrolled 386 patients without prior CAD who underwent 82Rb PET-MPI and invasive coronary angiography within 6 months, from 2010 to 2018. Abnormal shapes of stress left atrial blood pool (BP) time activity curve were characterized into five categories based on visual/quantitative assessment: (1) low stress/rest peak ratio (SRPR), (2) slow activity rise, (3) slow activity decline, (4) broad peak and (5) multiple peaks. The SRPR was defined as the ratio of peak count value on the stress BP activity by rest BP activity. A low SRPR was defined as one below the median value (0.82). We compared the diagnostic performance of stress MBF and myocardial flow reserve for detecting obstructive CAD (≥70% stenosis) using area under the curve (AUC) analysis. RESULTS:Among the five abnormal categories, the AUC of stress MBF in the low SRPR group (n = 193) was lower than in the normal SRPR group (n = 193) in per-patient (.67 [.59-.74] vs. .78 [.70-.84], P = .0499, respectively) and per-vessel analyses (.68 [.63-0.73] vs. .75 [.71-.79], P = .0352, respectively). The AUC in slow activity rise group (n = 167) for stress MBF was lower than in others in per-vessel analysis (n = 219) (.68 [.62-.72] vs. .75 [.70-.79], P = .0270). Other abnormal profiles showed no significant differences (all P > .05). CONCLUSIONS:Low SRPR and slow activity rise were associated with reduced diagnostic performance of stress MBF.

Background: Left ventricular (LV) mass is a well-established prognostic indicator for cardiovascular risk. Measurement of LV mass on coronary computed tomography angiography (CCTA) is considered optional. We aimed to assess for associations between LV mass measured on CCTA with all-cause mortality (ACM) risk and to determine age- and sex-specific distributions. Methods: We evaluated patients without known coronary artery disease (CAD) who underwent CCTA at a single center. We assessed age- and sex-specific distributions (10th, 25th, 50th, 75th, and 90th percentiles) of LV mass index. ACM, the primary endpoint, was recorded over a median period of 5.1 [interquartile range: 1.4-8.4] years. The association between LV mass and mortality risk was assessed using multivariable Cox models adjusted for age, sex, medical history, coronary artery calcium (CAC) score and CCTA stenosis. Results: 4187 patients (mean age: 61.9 +/- 11.7, 63 % male) were included. Male sex, African American ethnicity, Hypertension, CAC>400, and smoking were independent predictors of increased LV mass index. During the median 5.1 years of study follow, 265 (6.3 %) deaths occurred. Increased LV mass index percentiles were associated with increased risk of ACM. The addition of LV mass index percentiles improved discrimination and reclassification for mortality prediction over a model with age, sex, conventional risk factors, CAC score and CCTA stenosis severity (X-2 improvement: 22.68, NRI: 28 %, both p < 0.001). Conclusion: In a large sample of patients without known CAD who underwent CCTA, increased LV mass index provided independent and incremental prognostic value for all-cause mortality. Assessment of LV mass by CCTA, considering age and gender distribution, can be utilized clinically to identify patients with high myocardial mass.

BACKGROUND:The effects of evolocumab on the underlying coronary disease activity by positron emission tomography (PET) and coronary tree plaque composition by coronary computed tomography angiography (CTA) have not been described. OBJECTIVES:This prospective imaging study aimed to evaluate changes in coronary plaque composition on coronary CTA and coronary microcalcification, a marker of plaque activity, on 18F-sodium fluoride (NaF) positron emission tomography (PET) after evolocumab treatment. METHODS:This single-arm, prospective, open-label study enrolled patients with baseline extensive noncalcified plaque volume by coronary CTA (>440 µL overall coronary artery or >250 µL in any single plaque). All participants underwent baseline and 18-month follow-up coronary CTA and 18F-NaF PET. Disease activity was evaluated with 18F-NaF PET by maximum target-to-background ratios at the lesion level and by coronary microcalcification activity for the entire coronary tree. RESULTS:A total of 47 patients (age 61.8 ± 10.1 years, 87% male) and 196 lesions were studied. Twenty-three (48.9%) patients were asymptomatic, 16 (34%) presented with chest pain, and 8 (17%) presented with dyspnea. Four (8.5%) patients had a prior coronary artery disease history. At a mean follow-up of 18 months, there was no significant change in total plaque volume (716.2 ± 431.4 µL to 710.8 ± 456.2 µL, difference: 5.4 ± 97.4 µL; P = 0.705). Changes in plaque composition were observed, with a significant reduction in noncalcified plaque (607.3 ± 346.8 µL to 562.1 ± 337.3 µL, difference: 45.2 ± 63.8 µL; P < 0.001) and low-attenuation noncalcified plaque (37.1 ± 28.9 µL to 20.4 ± 15.4 µL, difference: 16.6 ± 23.5 µL; P < 0.001). In contrast, there was an increase in calcified plaque (108.9 ± 133.7 µL to 148.7 ± 175.3 µL, difference: 39.8 ± 56.1 µL; P < 0.001). There was a significant reduction in coronary microcalcification activity (1.35 ± 1.68 to 1.08 ± 1.37; P = 0.004) and lesion target-to-background ratio (1.73 ± 0.85 to 1.62 ± 0.83; P = 0.005). CONCLUSIONS:In stable patients with extensive noncalcified plaque volume at baseline, 18 months of evolocumab treatment was associated with a shift toward a lower risk quantitative plaque phenotype and reduction in microcalcification activity. (Effect of Evolocumab on Coronary Atherosclerosis; NCT03689946).

BACKGROUND:The application of hybrid stress single-photon emission computed tomography/computed tomography (SPECT/CT) imaging allows for the combined assessment of patients' exercise ability and coronary artery calcium (CAC) burden. The prognostic utility of this combined information among patients undergoing stress SPECT-myocardial perfusion imaging (MPI) remains incompletely understood. METHODS:To simulate the prognostic information that can be provided by stress SPECT/CT, we assessed 2435 patients undergoing stress SPECT-MPI and CAC scanning within six months of each other. Patients were grouped into four groups of descending stress test performance: those exercising greater than or equal to 9 minutes, exercising less than 9 minutes, undergoing pharmacologic testing while performing a walk protocol, or pharmacologic testing without walking. Patients were followed for all-cause mortality (ACM) over a mean of 9.0 ± 6.4 years. RESULTS:During follow-up, 291 patients (12.0%) died. There was a stepwise decrease in survival with poorer stress test performance and with increasing CAC scores. Mortality was consistently higher in patients with lower stress test performance among all CAC categories. Conversely, higher CAC scores were associated with increased mortality risk across all four stress test performance groups. Patients with CAC scores greater than or equal to 400 but exercising greater than or equal to 9 minutes had a mortality rate similar to patients with zero CAC scores who could not walk during pharmacologic stress testing (8.8 vs 8.0 per 1000 person-years, P = 0.898). A multivariable analysis identified stress test performance as the strongest adverse ACM predictor, followed by age and CAC scores. CONCLUSIONS:The combined assessment of stress test performance and the magnitude of CAC abnormality provides highly synergistic prognostic information among patients undergoing stress SPECT-MPI.

BACKGROUND:We aimed to investigate in patients with known coronary artery disease (CAD) whether plaque burden assessed by coronary computed tomography angiography (CCTA) can predict subsequent all-cause mortality (ACM). METHODS:Consecutive patients with known CAD who underwent CCTA and coronary artery calcium (CAC) scans for CAD evaluation were enrolled. Known CAD was defined as history of myocardial infarction (MI) or percutaneous coronary intervention (PCI). Plaque burden was assessed by CAC (categorized as 0-100, 101-300, 301-999, ≥1000), degree of stenosis (DS) (0-24 ​%, 25-49 ​%, 50-69 ​%, and ≥70 ​%) and segmental involvement score (SIS) (≤2, 3-4, 5-7, and ≥8) on CCTA. Multivariable Cox regression analysis was used to determine the association between plaque burden and ACM. RESULTS:963 patients were included (age 66.1 ​± ​11.5, 72.0 ​% male) of whom 707 had PCI, 586 had MI, and 330 had both. During median follow-up of 3.0 years (interquartile range 1.0-6.5), 91 patients (9.4 ​%) died. By Kaplan-Meier analysis, higher CAC score was associated with a higher risk of ACM (p ​< ​0.001), but DS and SIS were not. In multivariable Cox regression analysis, CAC scores 301-999 (HR:3.10, 95%CI:1.23-7.80, p ​= ​0.017) and ≥1000 (HR:5.81, 95%CI:2.25-15.04, p ​< ​0.001) along with age, current smoking, and aspirin use were independently associated with increased risk of ACM, but DS and SIS were not. CONCLUSION:In patients with known CAD undergoing CCTA, CAC score>300 was an independent predictor of ACM. CAC may provide additional guidance for the intensity of secondary preventive treatments than the degree of residual stenosis or the number of segments with CAD.

OBJECTIVE:To assess the relative predictors of mortality risk in a contemporary cohort of patients referred for stress single-photon emission computed tomography myocardial perfusion imaging in whom all relevant risk factors and cardiac-related comorbidities were evaluated at the time of cardiac stress testing. METHODS:We evaluated 15,662 patients undergoing stress single-photon emission computed tomography myocardial perfusion imaging between 2008 and 2017. Patients were observed for a median of 6.7 years for all-cause mortality. Patients were assessed for their mode of stress testing (exercise vs pharmacologic testing), myocardial ischemia, coronary artery disease risk factors, and cardiac-related comorbidities, such as chronic kidney disease. RESULTS:Age and pharmacologic stress testing, which was performed in 48.1% of our patients, were the most potent predictors of mortality. Moderate to severe myocardial ischemia, a traditional driver of mortality, was present in only 3.6% of patients. There was a stepwise increase in annualized mortality according to patients' number of risk factors (P < .001) or comorbidities (P < .001). After stratification of patients according to their mode of stress testing, this stepwise relationship of multimorbidity to mortality was noted only in pharmacologically tested patients. By contrast, the annualized mortality risk of patients undergoing treadmill exercise not only was low (<1%/year) but remained so even for patients with a high degree of multimorbidity. CONCLUSION:Patients referred for cardiac stress testing manifest a stepwise increase in mortality risk with an increasing burden of coronary artery disease risk factors and concomitant comorbidities. However, this stepwise increase is not observed in patients who perform treadmill exercise at the time of cardiac stress testing.

BACKGROUND:Cardiac sarcoidosis is an uncommon but potentially devastating manifestation of sarcoidosis, which is a multisystem inflammatory granulomatous disease. Although corticosteroids are the mainstay of treatment, given the number of complications associated with their long-term use, there is increasing interest in the use of steroid-sparing agents. Recent basic and translational studies have suggested a role for the mechanistic target of rapamycin (mTOR) pathway in cardiac sarcoidosis. METHODS:We identified 4 patients treated at the Cedars-Sinai Cardiac Sarcoidosis Clinic who had active cardiac sarcoidosis and contraindications to corticosteroid intensification. We sought to evaluate the role of mechanistic target of mTOR inhibitors on the change in cardiac inflammation via cardiac 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging. RESULTS:Of the 4 patients, 2 showed substantial improvement in cardiac inflammation on follow-up FDG-PET imaging after 6 months of treatment with an mTOR inhibitor but without corticosteroid intensification. There was a greater than 80% reduction in the cardiometabolic activity. The other 2 patients treated with an mTOR inhibitor had persistent evidence of cardiac inflammation on follow-up FDG-PET, necessitating an augmented treatment regimen. DISCUSSION:This case series represents the first clinical use of mTOR inhibitors for cardiac sarcoidosis, and it suggests that these agents may have a role in the management of cardiac sarcoidosis.

Background: There has been an increasing call for employing ultrashort exercise activity questionnaires as a clinical "vital sign". To-date, this has not been applied to patients undergoing cardiac stress testing. Methods: We evaluated 1136 patients who completed a one-item exercise questionnaire before undergoing stress SPECT myocardial perfusion imaging (MPI). This question asked patients to grade how much they exercise during daily life on a 11-point scale (0 = none, 10 = always). Patients were divided into four exercise activity groups based on their response: no, low, moderate, and high exercise activity. The results of this questionnaire were compared with patients' clinical risk profile, mode of stress testing (exercise vs pharmacologic), and exercise treadmill duration. Results: We noted a stepwise inverse relationship between exercise activity and patients' frequency of hypertension, diabetes, and obesity (P < . 001 for each). Patients with no reported exercise activity were more likely to complain of dyspnea. There was a stepwise increase in the number of patients performing treadmill exercise with increasing reported exercise activity (P < . 001). The duration on treadmill exercise increased in stepwise fashion with higher patient reported exercise activity (P < . 001). Conclusion: Our single-item, self-reported questionnaire was correlated with patients' risk profiles, their mode of stress testing, and cardiorespiratory fitness. These correlates, along with the pragmatic nature of this ultrashort questionnaire, and its built-in identification of patients who may warrant exercise counseling, augurs for adopting ultrashort questionnaires regarding exercise activity among patients undergoing stress MPI, and other cardiac imaging tests where functional capacity is not routinely assessed.